Editors Note: (November 16, 2017) Scientists have agreed that gene drives are too risky, according to the New York Times.
There is no genetic code. Not really. Every mature biologist knows it’s true.
Unfortunately, a few immature biologists don’t believe it. They are developing “gene drive” technologies that they believe enable them to reliably and permanently alter a fragment of “the code” in any life-form that reproduces sexually; and to guarantee that the altered piece of “code” will be transmitted to the next generation 100% of the time into perpetuity.
What it means is that an altered fragment of genetic code can be “injected” into a species, for good or ill, which is permanent and can, over a few generations, become universal—unable to be suppressed or removed regardless of any natural selection pressures whatsoever—until the end of time.
The changes caused by gene drivers takeover every individual in any species that has been targeted for modification. It takes about 10 generations, give or take. With insects, we’re talking a couple of years; with plants, a decade maybe; with humans, 300 years or so.
Gene drivers are all about changing an entire species forever and permanently—not just one individual with a genetic disorder, for example, or one generation of plants for another. It’s a higher level of intervention than conventional gene therapies and modifications.
A screw-up can extinguish a species in a relatively short period of time is how I understand the danger.
If anybody doesn’t understand what they just read, they shouldn’t worry. By the end of this essay, they will fully grasp why the scientists pursuing this course might be dangerously naive and could possibly unleash genetic pollutants that might someday kill us all.
These very smart people (some may actually be prodigies for all I know) plan to use gene drivers to exterminate vermin and eradicate insect-borne disease, for starters. They plan to make it impossible for agricultural pests to develop resistance to pesticides.
It all sounds great. But so did using the by-products of nuclear bombs as an energy source for our cities. Ask Japan how their state-of-the-art nuclear energy program turned out. Ask about Fukushima. Read my essay, Nuclear Power and Me, to learn more.
Gene-drive technologies are an existential threat to the long-term survival of life on earth, just like those tens-of-thousands of plutonium-loaded thermonuclear missiles, which a number of countries have buried a few hundred feet below the surface of the earth. The warheads on these missiles are going to rot someday, because no one can take care of them forever, and we can’t get rid of them. Their poisons—the most lethal known; a speck of plutonium dust can kill any human who ingests it—will leach into the soils; over thousands of years percolating plutonium will kill everything.
Genes—bad ones (or very good ones that turn out bad; oops!)—genes that can never die; genes that can’t be suppressed by natural selection; genes that are always passed on to the next generation under every conceivable scenario and every possible pairing of mates (no matter how mismatched) present potential nightmare scenarios for any species that possess them. Errant gene drivers can extinguish some species in a matter of a few years.
It is distressing to think that smart, young adults—I can imagine some younger than 35 who possibly lack basic common-sense (does it matter how smart they are?)—might right now be playing around with molecules of DNA they can’t possibly understand fully, because these molecules have a quantum side to their nature that can make their behavior unpredictable; even unknowable.
These young adults are messing around with very complicated structures and processes inside both molecules and cells that they can’t see, even with the best microscopes and the most sophisticated instruments. It’s possible that they might—even with the best intentions; the best lab protocols—screw things up big-time and possibly forever. We need maximum oversight over these researchers and the labs who employ them, now—not tomorrow or next year.
Every biologist knows that “genes” have a mysterious way of migrating between species, crossing boundaries, and behaving unpredictably. They have a way of escaping confinement structures. If we don’t understand why, what are we doing playing around and calling it research?
Editors Note (May 27, 2017): here is a link to a May 17, 2017 article in Science News about the role of jumping genes in the expression of genomes, which may be of interest to some readers.
Anyway, I urge readers to relax for now in the knowledge that they are about to learn some amazing things. I certainly did, writing this essay. And please remember: I am a pontificator, not a scientist.
Links are provided to verify anything written in my essays that people may have questions about. My pledge to readers is, as always, to be as accurate as possible and to correct mistakes should I make them or find myself being corrected by others. Yes, I’m smart, and I write good, too. Well, I’m trying, anyway; and getting it right is important to me. I’d say it’s my highest priority.
The genetic code that everyone talks about lives inside tiny spaces; one way to think about it is to imagine that it lives inside little rooms packed to the ceiling with sacks—bitty-bags stuffed full of strung-together bases—hiding in the center of every cell of every plant and animal (or disbursed throughout the cell in the case of most one-celled microbes).
It isn’t a code at all. It’s a reservoir; an inventory; a collection of templates—most broken into pieces; separated and scattered among the dozens of spiral tentacles in the vast aperiodic-crystal known as DNA.
DNA isn’t actually a crystal either; not really. Crystals are structures made from regular (periodic) arrangements of molecules. DNA, on the other hand, is a molecule, and it is constructed mainly from strings of chemical bases. It’s usually found in bundles alongside other DNA molecules. These bundles are called chromosomes.
During part of a cell’s life-cycle these DNA strings can sometimes be found tightly wound around little pieces of protein like fishing lines around spinning-reels. It’s a configuration that makes them compact; less intrusive—but easier to see under a microscope when they have been stained.
Inside any particular cell each chromosome of DNA is in some ways a little like a snowflake; no two are the same; no two are alike, not even close. But every cell in the body contains the same group of chromosomes; the chromosomes in each body-cell are identical to the chromosomes in every other body-cell.
Bases, by the way, (in case someone might be wondering) are chemical substances that turn into salts, when acids are poured over them. Many bases exist in nature, but only four (nucleobases) are found in DNA. These four bases are essentially one or two rings of carbon atoms with ammonia and vinegar-like side chains attached. Here are links for anyone who wants to look them up: adenine – thymine, and cytosine – guanine.
Forgive me for starting simple. Life-sciences are the most complicated sciences of all. What adds to the difficulty is that in most animals (and all people) the DNA involved in sexual reproduction is configured differently than the DNA in body-cells. It exhibits behaviors a little less like those found in other cells. In this essay we are talking about animal DNA, usually human, in body-cells—somatic cells; and we are talking about protein production.
This essay is not about stem cells, which develop into any and every kind of somatic (body) cell and germ (reproductive) cell. Except for liver cells, somatic cells don’t divide and reproduce themselves. That function is performed by stem cells, which start at conception and continue through life to replenish the human body. They live inside the tissues of adults and will be the subject of a future essay.
Another hard concept to grasp: inside every animal cell (and plant cell) are hundreds of DNA packed bundles (called mitochondria), whose DNA is not like the DNA in our sex-cells or body-cells, at all. The DNA in mitochondria resembles what one might expect to find in another as yet undiscovered species. It’s “coded” differently. Yes, it’s weird, but there are explanations.
Most scientists today believe that a long time ago our cells engulfed some bacteria; these foreign migrants from another world were simply unable to escape. Bacteria are small. A thimble-full of dirt can contain 50,000 species. It would require as many as 10,000 individuals of some strains to match in size just one of the microbes displayed in the illustration a few paragraphs above.
Scientists named the trapped bacteria-like life-forms inside our cells, mitochondria, after the Greek words for threaded granules; these granules make the cells they inhabit more robust, because they act like little batteries, boosting the energy in their adopted homes to help do the many tasks that cells do.
Click on this link for an easy to understand video of the overall structure of cells; or on this link to a YouTube Video designed to dazzle viewers by transporting them through an imaginary, animated world constructed to make real the complexity of a working, living cell.
And here is a link by an expert, if anyone is confused about the numbers of bases and chromosomes in humans, as many folks seem to be, including even myself, sometimes. It’s confusing, because there are different “codes”, different cell-cycle phases, different kinds of DNA molecules; and I haven’t even mentioned enzyme catalysis or polymerases (and I’m not going to, either, not yet, because it will only open a big can of worms I don’t want to deal with right now). But let me say this: without all this complexity, life forms as complicated as human beings would be impossible—codes or no codes.
The tools most people use to do science, especially physics, generally depend on mathematics and rigid, predictable rules. The life-sciences aren’t like that; not at all. Should my essay devolve into complexity, readers are free to bail. I’m going to try to keep the truths I’m sharing understandable to non-technical people. Who knows if I’ll succeed or not?
DNA can be thought of as a collection of pouches or bags stuffed with billions of copies of four basic substances, called bases. DNA is like a roomful of holiday bags, each filled to the brim with four different kinds of unfinished toys, like the ones in Santa’s workshops before Christmas. Each of the four kinds of toys are strung together in-line, one after the other—in no discernible order—in long, tangled spirals. These spirals are unimaginably long, and there are many dozens of them.
The toys in the DNA sacks are unfinished, unpainted, and undecorated. They really don’t look very much like toys, at all. In this analogy, the four bases might be imagined as four simple blocks of wood, each a different shape and size. And like we said, there are billions of these four blocks, at least in human cells.
Is DNA a big molecule? Yes, we already said that it was. It’s huge. But good luck to anyone who tries to find one. Good luck to anyone who tries to see one. No one has ever seen any molecule. No matter how large, molecules are too small to see, even with microscopes; and that includes DNA molecules, the largest and most complex molecules in nature. It takes a combination of high-energy light, amplification, and computer generated algorithms to produce useful pictures of what scientists think molecules look like. A computer-generated image is not the same as a brain-generated image stimulated by the act of looking with a pair of human eyes.
Forty-six molecules (strands or bags or sacks) of DNA contain the six billion bases (or blocks) of the human genome. Most of the time these strands are loose and disorganized; a diffuse mass of hard-to-see chromatin. (Their structure depends on what period the cell cycle is in.)
It has to be this way for the worker elves of the cell to gain access to the bases (the unfinished toy blocks) on which they will do their work. Only during the process of cell division do these forty-six molecules bind together and curl-up into the twenty-three chromosomes and the three billion base-pairs we learn about in high school biology class.
Researchers have technologies that can amplify what DNA molecules reveal, which they can manipulate with computer algorithms to form fuzzy pictures that are helpful to highly trained analysts; but it’s the best they can do, visually.
An early theorist, Erwin Schrodinger, (one of my heroes) said in 1944—before anyone knew what DNA was—that it must be an aperiodic-crystal. He gave a series of lectures, which later became the famous book, What is Life? It can be purchased for fifteen bucks on Amazon.com.
Schrodinger’s book changed my world view; my view of life; it’s one of the most prophetic works I’ve ever read. And it turns out, Schrodinger was absolutely correct. DNA bundles store billions of bases in more-or-less random—but definitely frozen—sequences.
Just as molecules arrange themselves inside crystals, the bases inside DNA molecules also have an order, yes, for sure, but it’s not a code; it’s not even a cipher; it’s merely a starting point for the most chaotic, complex, and messed-up process in nature—the creation of thinking, speaking, conscious life (and less capable life)—all formed from a relatively few not-so-simple materials.
Here’s another assertion that might be difficult for some readers to accept. Genes don’t really exist. There are no free-standing genes; certainly not in human DNA, anyway. What scientists call genes must be constructed; they must be built; they must be put together; they must be fabricated, collected, and transported by molecules, called RNA.
But RNA in all its forms (and there are many) is itself constructed from scattered templates that are hidden haphazardly like Easter eggs within the billions of bases strewn along the dozens of spirals inside a DNA bundle. RNA builds itself up by interacting with various sections of base sequences in the DNA and then copying those sequences by borrowing matching free-bases, which are floating everywhere in the medium of the cell’s nucleus.
RNA is much shorter in length and less stable than the DNA it models. But it doesn’t mutate as much as folks might expect, because it is also shorter-lived and reproduces less often. It’s more versatile, too; more agile, because it is single-stranded; DNA is double-stranded.
RNA, in all its forms, is the work-horse of cell functions; it is both the building material and the construction machinery used in many important cell structures, which perform the yeoman’s task of protein building inside cells.
It seems plausible to me that over a few hundreds-of-millions of years the possibly self-generated RNA sequences may have acquired—through accident, luck, and trial-and-error—the ability to select, copy, paste, and assemble short sections of random DNA bases, which every-once-in-a-great-while actually worked to help build the useful proteins that added survival advantages to their evolving hosts. Maybe RNA designed and built DNA in the first place, which it learned to copy and manipulate. We may never know exactly how.
One thing scientists agree on: one-celled life was already highly developed, complex, and flourishing by the time the new planet, Earth, reached its first billionth year. Earth is four-and-a-half billion years old. Life came on fast during extreme conditions vastly different than now. This fact is amazing. No one understands how.
It has taken three-and-a-half billion more years to get to humans and the space-traveling civilization we have now.
Thinking about RNA and DNA can be a frustrating circular process, much like the chicken or the egg problem; which came first? Most scientists today believe RNA came first, DNA later. Inside our cells, it is impossible to tell, but there is no denying that RNA’s diversity and flexibility make it by far the most likely candidate.
Many kinds of RNA live inside our cells. Some run around doing nothing. They simply try to survive inside the complicated universe that is the typical living cell in every animal, plant, and microbe. They are called selfish RNA.
Most RNA sequences are much less selfish. They are like Christmas elves who work day and night; some to open Santa’s bags to gain access to their contents; others to copy various sections from the strands of blocks inside; others to move the copied sections to an assembly area, where other elves glue the copied segments together to form new sequences—many of which, by the way, are very different from the original sequences that the RNA elves found inside Santa’s gift bags; inside the DNA.
Eventually, messenger elves transport the long strands of little blocks they copied and assembled; they move them away from the center of the cell; out to the gooey regions of the cell beyond its center, where other transfer elves are busy assembling (by threes) free-floating blocks (called bases, remember) and attaching these triplet-blocks (called anticodons) to single amino acids. The resulting structure is called transfer RNA (or tRNA, for short).
An amino acid is simply a ring or two of carbon atoms with amine (ammonia) stuck to one side and carboxylic acid (vinegar) stuck to another—plus some other simple stuff attached here and there to make each amino acid unique among all the others. Think of an amino acid as a colored necklace bead. Out of the five-hundred or so differently colored beads in nature, transfer elves in humans work with only twenty or so.
Stay with me now. You just read the most difficult sentence in the essay. These amino acids attach themselves like colorized necklace beads to triplet-blocks (anticodons) according to which of the three blocks (or bases) the transfer RNA (tRNA) is made from.
In the meantime, while all this other stuff is going on, the messenger elves are directing their long strands of copied-and-pasted blocks (bases) away from the cell’s nucleus (center) toward little triplet-body-handling factories (called ribosomes; ribo for triplet, soma for body), which live in the outer goo (the cytoplasm) of the cell.
At the same time, the transfer elves in the outer goo (cytoplasm) steer their three-blocks-plus-a-colored-bead assemblies—in humans these three-base combos and twenty or so colored beads can be arranged forty-eight ways—into these same ribosome factories, where they are matched-up to the blocks in the long strands that are being delivered from the cell’s nucleus (like cars in a choo-choo train) by the messenger elves.
Inside the ribosome factories, the triplet-blocks-plus-one-colored-bead assemblies, which have been constructed and collected by the transfer elves in the cytoplasm, are paired block for block (that is, base for base) to the long train of blocks that were collected, arranged, and carried by the messenger elves from the cell’s tiny nucleus.
As each transfer assembly triplet is matched-up three bases at a time to the blocks in the long messenger train, the single amino-acid bead that the three-block transfer assembly carries is ejected out of the ribosome factory. Assembly elves (think of them as molecular forces) secure each ejected amino acid bead to the next, one after the other—in the exact order demanded by the order (in threes) of the bases (blocks) in the messenger sequence—creating as they go an amino-acid-chain, or necklace.
Once the amino acid chain (necklace) is long enough (and remember: there can be as many as twenty or so different colors of amino-acid beads in each necklace, and each necklace can be almost any length at all—up to hundreds or even tens-of-thousands of beads—folding elves (again, these are molecular forces) go to work; they bundle up the amino acid chains into the shapes that will make them into proteins. Then other elves take over to deliver these protein toys to every child’s bedroom in the cell, which in this analogy lie inside the abyss of the cell’s cytoplasm (cyto means cell; plasm means goo).
Some of the protein toys will sometimes be gathered by other elves who might feel compelled to try to deliver them down the street to other homes in other neighborhoods by way of certain processes known as cell migrations. These migrations can bring healing to far-away injured tissues in other parts of the body, among other benefits. However, as I wrote earlier, stem cells that live inside the tissues of the body do the heavy-lifting of cell replacement and healing.
Here is a way to visualize a human cell: think of cytoplasm as the yoke of an egg. The nucleus (the center) is a tiny, hard to find collection of chromatin at the very center of the yolk where the nucleic acid (the bundles that are stuffed with blocks or bases) is stored. Yes, there are dozens of other structures that live outside the tiny nucleus in the yolk (cytoplasm) alongside the ribosomes—the factories essential for protein production.
But we’re not concerned about those other structures right now. Proteins are the most essential part of what our bodies are made from. Over 100,000 different proteins are required to construct a human being. Ribosomes are very important, because it is inside the ribosomes where proteins get started, so we concentrate on them first.
Think of the cell’s membrane as the “white” of the egg. It surrounds and protects the vital cytoplasm where the making of proteins takes place.
But a lot more is going on. And—I have to say this—the cells of most microbes (one-celled life, like bacteria and archaea) don’t look like the sunny-side-up cells of humans or most other animals and plants. For one thing, they are a lot smaller. They can be from 20 to 10,000 times smaller. They lack membrane-bound organelles; they lack a nucleus. They look more like little sandwich bags of loosely cooked scrambled eggs. Scientists call them, prokaryotes. (It’s Greek, meaning before they became fully formed kernels.)
As for the other structures that live inside our own eukaryotic cells (again, it’s Greek, meaning after they became kernels)—they make a fascinating study, but are beyond the scope of this essay. Click on the links in this post—such as the links in this paragraph—to access Wikipedia articles, YouTube videos, and other sources to learn more about them.
Phosphoric acid, which people have used for centuries to remove rust and to fertilize crops—it’s the concentrated clear syrup that makes Coca-Cola sting the tongue (carbon dioxide bubbles serve mostly to make the drink sparkle to the eye)—is what the DNA sacks (or strands) are made from. People who eat steak, consume goodly amounts of phosphoric acid. Early researchers always found this acid in the center of the cell; its nucleus. So they called it, nucleic acid.
Only later did scientists discover that the sacks were full of bases, crammed together into tangled masses of long, curly chains they called chromosomes (Greek, for colored bodies). Chromosomes stained well during lab experiments, which was fortunate for researchers, because color made it easier to see the chromosomes during the short periods of time when the genetic material in the cell’s center took on its distinctive form from out of the shapeless, invisible chromatin, where it lived.
It is by a curious twist of chemical engineering—to my mind, at least—that the bases don’t react with the phosphoric acid that anchors them. The DNA molecules don’t collapse into little piles of salt, like one might expect. Maybe they should; but here on planet Earth, they don’t.
In this sense—the sense in which our DNA is made from acids and bases—we are salt, or could be; we are potentially a very complicated salt, yes, but a salt nevertheless. Salt is at the heart of what and who we might become were it not for the miracle that makes life live.
Phosphoric acid (phosphate) sacks (or strands) are loaded with toy blocks (bases), so they need something sticky, like a sugar, to keep the blocks from falling out. The D in DNA stands for the sticky stuff—deoxyribose, which means sugar.
DNA is deoxyribonucleic acid. The sugar and acid, together, form the rails of the famous spiral staircase, upon which the rungs of bases are hung. It’s the most incredible structure in nature. It’s called the double-helix. Some people named Watson, Wilkins, and Crick won a Nobel Prize for figuring it out.
To give readers a sense of scale: If someone were to take the longest strand of the double-helix in our DNA (it’s in chromosome-one) and somehow increased its diameter to one-inch (the thickness of a large garden hose), the DNA strand—when pulled straight—would increase in length to 567 miles (about 40 miles longer than the distance between Nashville and Detroit). The bases (or toy blocks, as we’ve been calling them) would stack in pairs, eight-pairs-to-the-inch, along the entire 567 mile length of the hose. In this single chromosome, each of the nearly half-billion bases it contains would be about the size of a Tic-Tac breath mint; maybe a bit smaller.
Rosalind Franklin, the gifted X-ray crystallographer, who did the experimental research that led to the discovery of the double helix, died of ovarian cancer at age 37. The Nobel Prize Committee has a long-standing policy of not awarding prizes to people who have died. It’s why Irish physicist and mathematician John Stewart Bell didn’t receive a prize for his civilization-changing work on quantum-entanglement, after he suffered his brain hemorrhage in 1990.
In Franklin’s case it was doubly sad, because she was also doing important work on the molecular structure of viruses related to polio (funded by the United States Public Health Service), when cancer overtook her. Once again another scientist—this time her partner, Aaron Klug—received the Nobel Prize that she might have shared.
Had Rosalind Franklin survived to receive two Nobel Prizes—one for her work on the double helix and the other on the structure of polio virus—she would be a household name, like Albert Einstein or Francis Crick or Jonas Salk. She lived in a generation and a culture that devalued her; she was a woman who competed with men, some of whom may have undercut her and didn’t want anything to do with her, a few admitted. It was a different time, the 1950s. Who knows where the truth lies?
For Franklin, fame and fortune wasn’t to be. Blame cancer, a disease of the “genes”, which she sacrificed her life to understand by working daily with the deadly X-rays that helped her unlock the secrets of viruses and, most important of all, to finally pull aside the opaque curtain that was hiding the shape of the molecule of life: DNA.
Once the structure of the double-helix became known, the potential to store information in a molecular bundle constructed like DNA was immediately recognized—and it appeared to be unlimited. It is why everyone at first thought that the DNA molecule must be a code, like an old-fashioned computer tape.
I’ve suggested that DNA is not a code; neither is it a cipher. Some researchers view DNA more as a storage device and a starting point for processes—complicated processes—that have taken place inside every living cell for 3.5 billion years.
Yes, a group of three bases and an attached amino acid, properly transformed and manipulated by RNA elves inside little protein-making workshops called ribosomes, can help to fabricate and string together colored beads to make necklaces (chains). Chains of amino acids (polypeptides)—properly ordered and folded, again by RNA elves—can become proteins.
Scattered DNA base sequences inside a cell’s nucleus, its center, are a starting point for an involved and complicated process of selection, duplication, transformation, and fabrication before anything useful can happen; before proteins can be built and released for living. To think realistically about life, especially human life, people should be reminded that two-thirds of our bodies is water; two-thirds of what’s left is protein; the rest is mostly fat.
Proteins are critical. Unless proteins are made right and duplicated accurately, life-forms will drift; life will change—as it certainly has over the 3.5 billion years that cellular life is known to have lived upon the earth.
The process that goes on inside cells, instead of being thought of as a precisely executed computer code, might better be compared to the process of weather found on every planet in our solar system. Each planet can be identified by its surface weather, which starts from a kit of basic materials, and is amplified by an avalanche of environmental conditions and chemistries, much like the bases in our chromosomes, which are selected, copied, shaped and reshaped, configured and reconfigured by RNA elves and other characters we have yet to meet (because the science of the evolving genome—the genetic material—and the phenome—what animals and plants look like—is still young, and we understand less than the little we think we know about the complete process, at least so far).
The processes used to construct life forms by starting with the bases in DNA are analogous to the processes we observe on the planets of our solar system, where each planet creates its weather from the matrix of materials and thermal conditions that seem to define it. Each planet in our solar system has a characteristic weather profile that depends on a chaotic interplay of materials and environment unique to that planet.
Earth has weather; so does Mars and Jupiter. Those who study planets know immediately which planet is which, simply by observing its weather. From where we sit on the earth, each planet looks like its weather. Each has its characteristic atmosphere of unique colors and patterns. Weather is a planet’s phenotype; it’s what we see when we look.
That’s how it is with life forms, too. Each life form is the result of weather patterns inside cells, which give each animal, plant, and microbe its unique essence; its physical presence in the larger world where we live.
It becomes conventional wisdom to think this way about life forms, when one considers that identical twins—two humans who share exactly the same DNA—always display a variety of differences when examined closely. Identical twins never have the same fingerprints, for example. There are systems of weather occurring around their genetic material in every protein producing region in their bodies. Epigenetics is the technical term for the study of how it is that variations in phenomes occur in organisms that have identical genomes—that is, identical gene sequences.
The outcomes of these storms are never the same; two supposedly identical children do not always receive the same toys from the RNA elves who rummage through their shared bags (strands) of DNA for the bases they will copy and rework into proteins. Things get mixed up and turned around. One toy gets selected; another doesn’t; one is painted green; another purple.
It’s a chaotic process that produces life on the earth. It’s a process that cannot be described or predicted by mathematics. If it could, we might take the DNA from prehistoric bones to create the original animals. Jurassic Park would be more than a Hollywood fantasy, which is what the book, movie, and sequels were and are.
An animal cannot be constructed from its DNA alone. A lot more is required than a simple collection of sequences formed from four bases and frozen in a molecule of DNA. A lot more of life’s machinery is required. The RNA elves—millions of them, like colonies of ants—must do their work.
When the work is done, and a protein has been made and delivered, the path back is lost, forever. No way exists—or is even possible—to reconstruct the sequence of bases in the DNA that started the process that built the protein. The process is not backward compatible, according to Matthew Cobb, the British zoologist and historian, in his latest book, Life’s Greatest Secret. Not only are the DNA sequences not reachable from knowledge of the proteins alone, the processing steps that took place between the protein and the DNA are unknowable.
I don’t want to get too mathy, but think about this: sixty-four three-block (or three-base) sequences can in theory “code” for a mere twenty or so amino acids. It means that as many as three or four of those three-base sequences (the transfer elves we talked about earlier) can “code” for the same amino acid.
Reminder: four bases are all the choices DNA offers. Taken three at a time, they are more than enough to “code” for twenty or so amino acids. Get out the calculator, those who don’t believe it. 4 X 4 X 4 = 64. As mentioned earlier, humans have acquired over the eons 48 three-base combinations to work with. Bacteria, for another example, have 31 according to Matthew Cobb. We need less than two dozen.
Amino acid sequences long enough to form proteins can be hundreds to tens-of-thousands of acids long. Forget about how amino acid chains get folded properly to make proteins. How can anyone work backwards from a protein formed from thousands of amino-acid beads—each one of which might have been secured to any one of three or four different 3-way combinations of bases (or blocks)—and then go about the task of reconstructing from all those possible combinations the exact sequence of bases (or blocks) in the original DNA, with which more than a few random RNA sequences interacted to make their choices from billions of bases in the first place? Take a breath. There isn’t enough time in the universe to figure it out.
Raise the number “three” (or four, or five, or six, or two; it doesn’t matter) to the thousandth power on a calculator, those who may be having trouble accepting a possibly demoralizing fact. Most calculators will spit out the word, OVERFLOW. The number of possible sequences is impossibly large. It might as well be infinite.
There are thousands of chains of all different lengths and folding patterns. No one is going to reverse-engineer the DNA of a life-form as complex as a human being from its proteins; nor from its RNA elves; nor from its essential enzymes and catalysts; not anytime soon; not ever. It goes for dinosaurs, trees, or any other reasonably complex living thing—now or from the distant past.
Why do we have to reverse-engineer? Why not read the instructions right off the DNA itself? By now most readers must be starting to understand that the sequences necessary to build proteins are scattered among billions of bases. We can’t find the right ones in the right order. It’s not possible; not for creatures as complex as humans or dinosaurs.
Even if someone could reverse-engineer DNA sequences from proteins, how would they construct and organize the ant-like colonies of RNA elves that must sort through the DNA bases to select and build the right sequences; how do they identify and isolate the sequences necessary to build and orchestrate, for example, the tens-of-thousands of enzymes that are required to give researchers any chance at all to build a functioning human-being or even a prehistoric dinosaur?
Now might be a good time to mention that there are virus infections that can alter the DNA in cells. These viruses are called retroviruses, because they reverse the DNA to RNA transcription process we discussed earlier by introducing an enzyme called reverse transcriptase into the cells they infect. This process is disease producing—it causes cancer—and destroys the host animal (or person) if left untreated. The enzyme, reverse transcriptase, has become a tool that molecular engineers now use to modify organisms in experiments. Enough said. The weeds of molecular biology grow thick and deep.
We used to believe we could clone animals from their DNA sequences alone. Yes, there once was a cloned sheep named Dolly. Some readers may have read about her. After many heart-breaking failures, researchers managed to take the DNA from the mammary gland of one sheep, inject it into the nucleus of an egg from a second sheep, and implant this DNA cocktail into the womb of a third. By some miracle, Dolly was conceived and born, on July 5, 1996.
Sheep live twelve years, on average. By Dolly’s fourth year arthritis crippled her. At year seven researchers euthanized her; she had developed a chronic and incurable lung disease. Dolly was the recipient of arguably the best healthcare any sheep ever received in the history of veterinary medicine. She didn’t do well. Click this link for an update on the Dolly research.
For the sake of complete accuracy, permit me to admit that no one I know clones sheep anymore. There are too many failures. The failure rate for clones is right around 100%. Clone researchers, as far as anyone knows, have never used DNA alone, anyway. All borrow the enzymes, RNA, ribosomes, and other cell structures of other life forms to incubate the DNA they play with to try to create “artificial” life.
And speaking of enzymes, can we please not go there? I’m reminded of Chris Farley in the 1992 movie, Almost Heroes. Does anyone remember? His tutor asks him to try to learn the symbol for lower-case A. “What do you want from me?” Chris roils his eyes while clawing at his hair. “Do you want my head to explode?!”
Well, no, of course we don’t. But for those who have to know more, why not push ourselves just a little bit harder? May I point out the obvious? Enzymes speed up chemical reactions. A chemical reaction that might under normal circumstances take years can be reduced to milliseconds by an optimally-configured enzyme.
Some enzymes are made from RNA; most are proteins; in fact, most proteins are enzymes; they all get their start from sequences of bases hidden deep within the mountains of DNA inside our cells. These bases are selected, copied, and transformed into their many convoluted shapes for a very special reason: to help accelerate over 5,000 processes inside our cells.
Without these highly specialized structures, our metabolism would grind to a halt; our DNA and RNA would acquire all the mobility of a conga-line of standing stones; it would freeze into a petrified forest of non-living complexity. Life as we know it would be impossible; code or no code.
Here is a good question: Has any research team ever created artificial life in a laboratory?
Craig Venter, who has been interviewed on 60 Minutes and appeared in several Ted Talks videos, says that he has. He oversees a number of research labs funded by big oil and the government. His labs write computer code to generate base sequences, which they construct and then inject into yeast (among other techniques) to produce forms that they hope will someday lead to bio-fuels and green-house gas inhibiters.
Among other accomplishments, one of the labs, the Craig Venter Institute, is known to have introduced a gene from the bacteria, escherichia coli, into the earth’s toughest microbe, “Conan the Bacterium” (Deinoccocus radiodurance), to create microbes that can detoxify radioactive wastes at nuclear facilities.
So the answer to the question about whether anyone has ever created artificial life must be, Probably not, not really—not from scratch, anyway.
In 2012 a different group of researchers did find a way to arrange a set of very different bases inside DNA-like molecules called XNA. But it was a way of coding sequences only; it didn’t produce or even arrange proteins into anything that could be called, alive.
XNA is the precursor, many hope, for long-term storage of massive amounts of information in small, stable molecules—demanded now by data-churning behemoths such as CERN, home of the world’s most powerful particle-collider, located in Geneva, Switzerland.
The fact that artificially constructed molecules like XNA can store useful information does not mean that DNA does the same. People have imagined meaning into the bases of DNA, which they simply don’t have—to help better understand their function and to more effectively manipulate them—for good or ill.
Another development in 2012, which some readers may remember, is that researchers learned to use a technique known by the acronym CRISPR to change the sequence of bases in stretches of DNA. These scientists insist that gene “therapies” are desperately necessary, because the fact is: DNA is defective—most of it. Very few humans are symmetrical, attractive, disease-free, smart, emotionally stable, long-lived, or any other desirable thing anyone might think of that is caused by how we are built or how we are “coded” at a molecular level.
Gene drivers (mentioned in the first paragraphs of this article) are being developed in coordination with CRISPR techniques to enable changes to DNA molecules that will be permanent and transmittable 100% of the time. Their success will depend on how well we understand what is going on inside the molecules of life; and inside our cells.
Editors note: In January 2018 researchers admitted that problems related to positional locating have created a roadblock to success for CRISPR technologies. They hope to solve the problem soon to avoid a catastrophic failure in the application of this heralded gene-altering technique.
I believe we need to slow down and learn more before we unleash immortal genes into the biosphere that we can’t pull back and may turn out to be harmful, despite our best intentions. Asilomar style conferences with the force of international law behind them are desperately needed to control bio-technologies that are quickly getting out-of-hand and beyond the control or understanding of government and politicians.
It is quite certain that PCR technology (polymerase chain reaction amplification), which scientists use to amplify and detect the molecules of DNA-style life might be misleading folks into believing that DNA-style life is all there is. The earth could be infested with non-DNA based life, but no one will ever know until other technologies capable of observing it are developed and perfected.
People need to remind themselves that we are talking about molecules here—molecules of life that can’t be seen; even with the help of the most sophisticated microscopes. Everything science knows comes from amplification techniques and mathematical analyses. I hope someday to write an essay on the techniques scientists use to tease out what they know for sure about these impossible-to-observe molecules.
Serious scientists refer to the possibility for the existence of non-DNA style life as the “shadow biosphere.” If this non-DNA life interacts with our own in a symbiotic way, the potential for harm, it seems to me, increases the more we play around with molecules we don’t fully understand, while we remain oblivious to life we can’t detect, because we lack appropriate laboratory tools and techniques.
We don’t know what we don’t know; and what we don’t know can kill us all, if we aren’t cautious. Researchers might be walking through a genetic mine-field, but are so eager to cross that they ignore the danger of amputated limbs; the loss of sight and hearing; the possibility of disfigurement to the genomes of species like our own, which we may one day come to regret.
No human is perfect. Sometimes our imperfections are caused not by bad stretches of DNA but by naughty RNA elves who copy less than optimal sections of bases, which they hammer together into less than optimal genes, which can screw-up a sequence of amino acids. The RNA elves end up making defective proteins that pollute our cells, damage our bodies, and make our lives miserable.
To the extent that these screw-ups are the result of a lousy sequence of bases in our DNA, these patterns are likely able to be altered using CRISPR technology (if anyone can get it to work right), which is likely to increase the odds of inducing better outcomes. But many screw-ups, perhaps most, are not caused by poorly sequenced genes constructed from our DNA.
Many problems result from bad choices made by some arbitrary RNA elf, for example, who might have decided, perhaps, to cut and paste a random mix of bad sections it rummaged from the DNA strands; its errors and mistakes might not always be able to be located, identified, and repaired successfully. Renegade RNA elves are hard to track down and fix; at least so far.
Some problems can be caused by all kinds of things not related to DNA, like temperature, quantum effects, and cosmic radiation, including sunlight. The number of things that can go wrong with the weather-environment inside our cells is enormous.
It’s probably a contributing factor to why our haystacks of six-billion DNA bases hide a mere twenty-one thousand so-called genes, most of which are scattered in pieces throughout our vast DNA bundled-network. Those few sequences that are important to our survival are less likely to be attacked and mutated, if they are surrounded by sequences of little or no value to survival and good health. These base-sequences hide like proverbial needles in the haystack.
Big chunks of DNA are thought to be junk—relics left behind by billions of years of evolution and change. Junk DNA could be a legacy of screw-ups and obsolescence. Dolphins, for example, have noses, but can’t smell. They seem to have a lot of corrupt DNA sequences related to smell, which are broken and don’t work, due to neglect and disuse.
Humans are no different. We have DNA we no longer use. Through disuse, our base sequences, some of them, get corrupted over time and become unusable. The base sequences don’t get up and go anywhere, though. They just hang around, paralyzed, doing nothing. They become unrecognizable to the RNA elves, who learn somehow to avoid them.
A Russian agronomist from the Soviet era, renown in his time as an expert on the cultivation of wheat, Trofim Denisovich Lysenko, believed that organisms under stress could draw on reserves from what we today call junk DNA to change their hereditary tendencies and enhance their survival odds. His idea has yet to be discredited.
The simple onion has seven times as many bases in its DNA as humans. The loblolly pine tree—it’s an important source of lumber, which thrives in southern swamps—houses twenty-one times as much DNA as people. What do all these bases code for? They code for nothing, apparently. Maybe they are a warehouse of survival tools left behind, as the distant past of billions-of-years ago gradually transforms itself into now; our miraculous present.
Another compelling idea that occurred to me as I wrote this essay is that the tangled mess of unused DNA in every organism might have grown both in volume and complexity during ancient times—quite apart from environmental pressures on the organisms themselves. Could massive DNA growth have preceded evolution, which enabled and accelerated bio-diversity during unpredictable environmental catastrophes?
Is it possible that mammoth reservoirs of disorganized and unused bases that grew and multiplied inside the nuclei of ancient cells—much like molds in petri dishes—might be the enablers that fueled explosions of diversity and complexity in organisms during times past? An abundant supply of unused DNA combined with aggressive colonies of swarming RNA segments might help to explain rapid, diverse bio-blooms (and even account for absences in fossil records) that seem to have occurred during the Cambrian era—to cite one example out of many.
Many of the world’s smartest people are just getting started in the field of molecular genetics. Despite all that’s been learned by others, there is much more to know; much more to discover and understand; perhaps processes we haven’t considered that produced the enormous biodiversity of planet Earth.
DNA bases are not a code, it seems to me; they are simply a platform for departing mRNA trains that, when properly coupled, can become assembly templates for chains of amino acids—complex assemblies of molecules that depend on very many processes and structures in order to have even the remotest chance of being transfigured by ribosomes into an infinity of unlikely proteins—matrices of proteins and other structures, which seem to rise from the dust and the seas like the miracles of angels; an endless froth of bubbles; a deluge of cells that have, over eons, shaped the messy, sometimes ugly, often beautiful human beings and all the other life on our planet; our home; our beloved Earth.
In 2015, the University of Manchester zoology professor, Matthew Cobb, published an incredible book: Life’s Greatest Secret. Science celebrity, Brian Cox—in typically British understatement—labeled it, “a bloody brilliant book.”
Adam Rutherford, the British geneticist said, “This is the definitive history of arguably the greatest of all scientific revolutions.”
Life’s Greatest Secret is a must read for anyone who is interested in the science and history of the human genome. We strongly advise our readers to buy and read this important book. Billy Lee has read it twice, marking it up each time with magic-marker and margin-notes. It is a science block-buster; a fantastic book written in an engaging, easy-to-understand style.
The Editorial Board